India, Emerging Infectious Disease and the One Health Framework

http://www.onehealthinitiative.com/map.php

The concept of ‘One Health’ promotes the realization that the health of humans, animals and the environment are linked to each other.

Animals can be sentinels of environmental hazards for humans; for example, regularly monitoring the levels of dangerous contaminants (eg lead) in pets can alert to the potential for poisoning of children. Animals develop many of the same diseases we do and can thus be good model systems. For example, dogs live for about 20 years making possible long-term longitudinal studies to assess cancer risk as exemplified by the Golden Retriever Lifetime Study. The discovery that ticks transmit cattle fever germinated the idea of mosquito bites transmitting yellow fever and malaria. Antimicrobial resistance in humans is directly traced to the use of antibiotics in livestock and poultry.

Animals are an affordable and sustainable source of protein for humans. But food security often comes at the risk of deforestation, which can promote the spread of emerging viruses to humans. Ebola and SARS viruses are directly transmitted to humans through eating infected wild animals. Nipah virus was traced to pigs that were reared on deforested land and got infected from fruit bats emerging from the lost forest. Researchers are also exploring the role of pigs as intermediate hosts in the transmission of Ebola virus.

In a landmark report in 2008¹, Kate Jones and colleagues (Zoological Society of London, UK) analyzed emerging infectious disease (EID) events between 1940 and 2004, with some startling conclusions. The EID events had a non-random geographic distribution, were dominated by zoonoses (i.e. transmission from animals to humans) of which over 70% originated in wildlife, and their origins correlated with socio-economic, ecological and environmental factors.

Of almost 1500 pathogens known to infect humans, over 60% are of animal origin. But these ‘known’ knowns appear to be a small fraction of the total diversity. A 2013 study estimated 320,000 viruses to infect mammals; if extrapolated to other species, there are an estimated 100 million viruses on our planet². There is thus a vast pool of ‘unknown’ knowns.

What infectious agents are lurking in animals that can jump into humans and cause disease? Are we at a greater risk of zoonoses from apes, which share our genes, or rodents, which share our habitats? With the devastating track record of zoonotic pathogens such as HIV, pandemic influenza, Ebola and others, it would be sensible to address this comprehensively.

Two recent studies^3,4 report on viruses spilling over from animals into humans and what drives such zoonotic risk.

Olival and colleagues (EcoHealth Alliance, USA) writing recently in the journal Nature³, analyzed associations between 754 mammals and 586 viruses to understand what determines viral richness, diversity and zoonotic potential. Bats, primates and rodents were found to carry the highest numbers of zoonotic viruses. Bats are also a major reservoir for coronaviruses, which made big news in 2002 when SARS emerged in China, spreading to 27 countries and killing 774 people. In 2012, the newly emerged MERS coronavirus caused 640 deaths.

Anthony and colleagues⁴ (Columbia University, USA) studied coronavirus diversity in 12,333 bats, 3,387 rodents and 3, 470 monkeys from 20 countries in Central Africa, Latin America and Asia, which were previously identified by Jones as ‘hotspots’ for zoonoses. Nearly 10% of bats carried coronaviruses compared to only 0.2% of the other species, with diversity being highest in locations that harbored multiple bat species, such as the Amazon rainforest.

India also has an an incredibly diverse bat population with 117 species and 100 sub-species⁵. But we know nothing about the viral diversity that it harbors and its potential for causing human or animal disease.

The Jones study should have alerted researchers and health policy people in India. We and our immediate neighborhood are ‘hotspots’ for zoonotic, drug-resistant and vector-borne pathogens. But there is little information from India, a key country that is also missing from the Anthony study. Poor domestic research and international collaborations in this area, the latter driven by restrictive government policies on sharing clinical and research materials, are responsible for it.

Professor Ian Lipkin at Columbia University is a world expert in the search for novel pathogens and a key contributor to the Anthony study. He has also tried to work with India for many years. “Sample access is challenging”, says Prof. Lipkin. He adds - “I'm eager to help (provided) the logistics can be sorted. Let's focus on technology transfer in emerging infectious diseases. Global public health and the people of India deserve our best efforts”. 

Why is India an EID ‘hotspot’?

The transmission of infectious disease requires contact, and its probability increases with population density. With a population of 1.34 billion people⁶, 512 million livestock and 729 million poultry⁷, and a land area of 3.287 million sq km⁸, India has a high density of about 400 people, 156 livestock and 222 poultry per sq km. High rates of human-animal, animal-animal and human-human contacts increase the potential of emergence, circulation and sustenance of new pathogens.

The International Livestock Research Institute in Nairobi, Kenya, showed 13 zoonoses to cause 2.4 billion cases of human disease and 2.2 million deaths per year. The highest zoonotic disease burden, with widespread illness and death, is on Ethiopia, Nigeria, Tanzania and India⁹.

India has also lost about 14,000 sq km of forests over the past three decades, bringing down its forest cover to 24% of land area¹⁰, against the recommended one-third. This increasingly brings wildlife into contact with humans and domesticated animals, adding to the direct risk of zoonoses from wildlife. Forest loss also alters weather patterns, indirectly and unpredictably affecting zoonoses.  

India presents a poor picture of One Health research, preparedness and policy.

There are 460 medical colleges and 46 veterinary colleges in India, but most do little or no research. Limited research on priority zoonoses such as influenza, tuberculosis, encephalitis and others, happens primarily in the health sector, with the veterinary sector paying little attention to human disease.

The governance structure and inter-sectorial coordination is also problematic. The work on human health is guided by the Ministry of Health and Family Welfare, that on animal health and husbandry by the Ministry of Agriculture, and on the environment by the Ministry of Environment and Forests. Each works in a silo.

India’s National Health Policy¹¹ approved recently is also a missed opportunity. Framed to address the changing national healthcare needs, it does not even mention the terms “zoonoses” and “emerging infectious diseases”. It fails to break down the sectorial silos or provide an enabling environment to build core capacity in key EID areas.

What must India do?

India has shown that various sectors can successfully come together in a crisis situation such as during the 2006 Bird Flu outbreak. The need is to move from being reactive to proactively understand zoonotic pathogens before they emerge as disease in humans. This will require preparedness and policy inputs.

An Inter-Ministerial Task Force involving the key sectors of science and technology, human and animal health and the environment could be entrusted with preparing a policy framework that enables preparedness by strengthening research and health systems. Life scientists, physicians, veterinarians and ecologists could be awarded collaborative research grants to comprehensively survey animal species for pathogens with potential for causing disease in humans.

The technology for pathogen discovery is not complicated and is also available in the interest of global health. The challenge is to come together.

Such research also makes economic and political sense.

Discovering the entire viral diversity on Earth is estimated to cost $6.4 billion². In comparison, the World Bank estimates the 2002 SARS outbreak to have cost the global economy $54 billion, and a severe flu pandemic could cost about $3 trillion or 5% of the world economy¹².

A new disease emerging in any part of the world is a global threat. If India aspires to be a future leader, it must take this responsibility seriously. After all, if we can pledge to not proliferate nuclear weapons, how can we remain a potential threat for disease proliferation?

  

References:

1     https://www.nature.com/nature/journal/v451/n7181/full/nature06536.html

2     http://mbio.asm.org/content/4/5/e00598-13

3     https://www.nature.com/nature/journal/vaop/ncurrent/full/nature22975.html

4     https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5467638/

5     http://ibcru.org/bats/

6     http://www.worldometers.info/world-population/india-population/

7     http://www.nddb.org/information/stats/pop

8     https://en.wikipedia.org/wiki/Geography_of_India

9     http://www.natureasia.com/en/nindia/article/10.1038/nindia.2014.97

10   http://www.indiaenvironmentportal.org.in/media/iep/infographics/how%20much%20forests%20left.html

11   http://mohfw.nic.in/sites/default/files/9147562941489753121.pdf

12   http://www.cnbc.com/2014/02/05/counting-the-costs-of-a-global-epidemic.html

Discussing viruses in Napoleon's backyard

I just returned from Ajaccio (pronounced Ajak-cio) on the western coast of the island of Corsica, a French territory in the Mediterranean Sea, which is actually closer to Italy than it is to France. Besides being an extremely beautiful locale, its claim to fame is being the birthplace of Napoleon Bonaparte.

The purpose of this trip was to attend a meeting of the International Consortium on Antivirals (http://www.icav-citav.ca/), "a not-for-profit drug development organization dedicated to the discovery and development of anti-viral therapies for neglected and emerging diseases." This was a small "by invitation" conference with scientists from various parts of the world who discussed emerging viruses, neglected diseases and strategies to fight them over 3 days.

Most of the group traveled from Marseille to Ajaccio (map on left), an overnight journey on the ship Napoleon Bonaparte. I flew from Delhi to Paris, on to Ajaccio to land at the (you guessed it right) Napoleon Bonaparte airport. Ajaccio, the capital city of Corsica is at the northern end of Ajaccio Bay (map on right). The conference was in Ajaccio, but we stayed at a resort called Coralia Club across the Bay at Porticcio (map on right), about 20 km by road or a 15 minute ferry ride across the Bay.

Ajaccio Bay is beautiful with hills lining it all along. It makes for a perfect setting to watch the sunset, and if you can get up early enough in the morning when the moon is full, it offers a spectacular sight. The pictures below show various moods across Ajaccio Bay, from Ajaccio and Porticcio.

Corsica is the fourth largest island in the Mediterranean Sea, with a coastline of over 1000 km and a population of only around 250,000. Large parts of the island are Nature Reserves, which includes rare breeding sites for sea eagles and protection for other endangered species. Corsica has been inhabited continuously since the Mesolithic Age and over time acquired an indigenous population that has influenced Mediterranean history. It became part of the Roman Empire, and was claimed by the Repulics of Pisa and Genoa. The Genoese took possession in 1347 and governed till 1729, briefly being taken by the French in 1553. The Corsican Independence Movement began in 1729 and 26 years later, in 1755 an independent Corsican Republic was formed under the leadership of Pasquale Paoli, which remained sovereign till 1768. In 1764, Corsica was secretly purchased by the French from the Republic of Genoa. Following a  brief civil war in 1768-69, Corsica was incorporated into France in 1770.

Napoleon Bonaparte (Nabulione Buonaparte) was born in 1769 in the house of Charles-Marie Buonaparte, an attorney and secretary to Pasquale Paoli. The modest 4-storey home is now a museum in the heart of Ajaccio, not far from the central piazza, the cathedral and the Town Hall.

The central piazza has a statue of Napoleon on horseback surrounded by his four brothers. Napoleon's presence is all over this town in the form of statues, streets and lanes.

Travel to the northern point of Ajaccio Bay and you come across some interesting sights. At lands end the coast is rocky and the Sanguinaires archipelago is visible with its Genoese tower, which was used to sight pirates and warn the inland population by lighting fires. Similar towers can also be found inland to relay the message through smoke and drums.

Another very interesting and unique sight towards the northern end of Ajaccio Bay is the Cemetery. It is unique because unlike other cemeteries with graves, this one has small chapels, each for an individual or many times even for a family.

While strolling through the Cemetery, I captured an interesting view with the chapels in the foreground and modern apartments in the background. I call this "Apartments for the Dead and Living".

The beauty of this place is awesome. I forget I was actually here to discuss viruses, viral diseases and research on drugs against them. So, back to the science.

The Conference was held at the Palais des Congres, which overlooks the Ajaccio Port. The first session presented an innovative model for funding drug development research. This included adding a small tax on international travel, which has so far raised over $500 million to finance access to medicines in developing countries.

The session "HIV - Present and Future Challenges" discussed various aspects of HIV vaccines, including recent success of the ALVAC-AIDSVAX prime-boost vaccine combination (which I covered in an earlier blog; Sept 24), and the failed Merck vaccine trial last year. Discussions also  focused on the host response to HIV infection and ways to modulate the host to contain infection.

The session "Dengue - An integrated model for arthropod-borne viral disease control" was dominated by an elegant and comprehensive talk by Eva Harris from UC-Berkeley. Eva's efforts from the bench to bedside in dengue research, her reach in impoverished and under-developed scientific communities, and her efforts to make them part of the solution are truly inspiring. Various other lectures and discussions focused on new drug targets in dengue and other flavi viruses. The community seems to be coming together for drug design and testing that requires coordination between virologists, structural biologists, bioinformatics experts, organic chemists, industry and clinical trials experts.

The sessions on "Emerging Viruses" started with  an entertaining but highly informative talk by Ernst Gould from Oxford University. Ernie's appearance and mannerisms reminded me of one of the comedians on the very funny TV show "Whose Line Is It Anyway". Various other speakers dealt with drug design efforts against hepatitis C virus, influenza virus, and more generic approaches to broadly active drugs against positive- or negtive-stranded RNA viruses. Predictably, pandemic flu viruses dominated the discussions.

This is definitely one of the best meetings that I have attended in a long time. Besides the beautiful surroundings, the science was good, discussions were intense but friendly and informal, the organization was superb, and there were just enough people to make it scientifically interesting yet personal.

One advantage of meeting in a small place is that even scientists get noticed. The Mayor of Ajaccio organized a reception for us in the Town Hall. We passed through a ceremonial Guard of Honour and were welcomed and addressed by the Mayor himself in the richly decorated Napoleon Bonaparte room.

The ICAV recognizes the state of scientific research and the pharmaceutical industry in India, and expressed interest in starting an India Consortium. A few MOUs were signed between ICAV and Indian institutions. We return energized from this conference and hope to get more Indian colleagues involved in this unique effort. We also hope to organize the 2011 ICAV Annual Conference somewhere in India.

I would like to personally thank  the organizers for inviting me and a few other colleagues from India. Jeremy and Michel are the brains behind ICAV; Rajan and Christine did all the logistics. Thank you everyone for a wonderful and stimulating meeting.

I hope to see you all in Montreal next year.